Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment

João Conde, Nuria Oliva, Mariana Atilano, Hyun Seok Song, Natalie Artzi

Producción científica: Artículo en revista indizadaArtículorevisión exhaustiva

220 Citas (Scopus)

Resumen

The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs - a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor) - provides outstanding capability to synergistically abrogate tumours. Conjugation of RNA triple helices to dendrimers allows the formation of stable triplex nanoparticles, which form an RNA-triple-helix adhesive scaffold upon interaction with dextran aldehyde, the latter able to chemically interact and adhere to natural tissue amines in the tumour. We also show that the self-assembled RNA-triple-helix conjugates remain functional in vitro and in vivo, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.

Idioma originalInglés
Páginas (desde-hasta)353-363
Número de páginas11
PublicaciónNature Materials
Volumen15
N.º3
DOI
EstadoPublicada - 1 mar 2016
Publicado de forma externa

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